Intravascular microstructural, chemical and biomechanical characterization of coronary plaques

冠状动脉斑块的血管内微观结构、化学和生物力学特征

• 批准号: 10669254
• 负责人: Nestor Uribe-Patarroyo
• 金额: $ 72.83万
• 依托单位: MASSACHUSETTS GENERAL HOSPITAL
• 依托单位国家: 美国
• 财政年份: 2022
• 资助国家: 美国
• 起止时间: 2022-08-01 至 2026-04-30
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10669254
• 关键词: Address; Angiography; Arterial Fatty Streak; Atherosclerosis; Biomechanics; Cadaver; Cardiac; Catheterization; Catheters; Cause of Death; Cessation of life; Chemicals; Clinical; Clinical Research; Consumption; Coronary Arteriosclerosis; Coronary artery; Coronary heart disease; Development; Disease; Distal; Elements; Environment; Event; Family suidae; Funding; Future; Goals; Heart; Heart Diseases; Human; Image; Imaging Device; Imaging technology; Intervention; Lasers; Lateral; Lesion; Link; Measures; Mechanics; Methods; Modeling; Molecular; Myocardial Infarction; Near-Infrared Spectroscopy; Obstruction; Optical Coherence Tomography; Optics; Pathology; Pathway interactions; Patients; Procedures; Property; Research; Resolution; Risk; Robotics; Rupture; Source; Specificity; Speed; Stents; Structure; System; Techniques; Technology; Testing; Thinness; Time; Translations; Validation; biomechanical test; coronary plaque; elastography; human subject; imaging platform; improved outcome; individual patient; instrumentation; meter; novel; optical imaging; optimal treatments; percutaneous coronary intervention; preventive intervention; response; signal processing; technology development; technology validation; tool; treatment strategy

Heart disease is the leading cause of death in the US; the most prevalent type of heart disease is caused by atherosclerosis, the thickening of the vessel wall and creation of atherosclerotic plaque. Intravascular optical coherence tomography (IV-OCT) has enabled the imaging of coronary artery structures with un- precedented detail, and can be used to evaluate the response to percutaneous coronary intervention when treating atherosclerotic lesions. However, there remains a significant need to assess plaque vul- nerability: the determination of which mild lesions are likely to produce cardiac events in the future, and thus require immediate preventative interventional measures. Among lesion types, thin-cap fi- broatheromas (TCFA) are of particular concern since they are believed to be at increased risk of rup- ture; however, studies have found that only a fraction of TCFAs rupture. Although the likelihood of rupture has been linked to its mechanical stability, its chemical composition, and its microstructure, there is currently no technology capable of the biomechanical profiling of plaques in individual patients during intervention [without the need for time-consuming finite element modeling (FEM)] and the available methods for determining composition either lack specificity or spatial resolution. To address this significant need unmet by current intravascular imaging technology, we will develop an all-optical imaging platform that will profoundly broaden the access to accurate biomechanical, chemi- cal and microstructural profiling of coronary plaques in individual patients. Our novel platform will en- able a transformational leap in the current capability for comprehensive plaque characterization, in- cluding the assessment of plaque composition and vulnerability. We will leverage new ultra-fast laser sources to develop IV-OCT at 2,000 frames per second, enabling a host of powerful post-processing techniques that will enhance comprehensive characterization of plaques. In Aim 1 we will develop the enabling hardware to realize high-speed intravascular imaging. In Aim 2 we will develop hardware and signal processing to enable microstructural profiling at the 10×302 µm3 (depth×lateral) scale, chemical profiling at the 80×802 µm3 scale, and biomechanical profiling at the 60×602 µm3 scale in an all-optical technique without the need for FEM. In Aim 3 we will develop a novel validation platform based on a soft-robotics cardiac simulator of the biomechanical environment of the human beating heart. Our single imaging platform will facilitate clinical studies to determine the parameters of plaque vulner- ability, opening the door to the identification of optimal treatment strategies. Initially, it will become an invaluable research tool in atherosclerosis; later, it will have the potential to guide intervention in indi- vidual patients. After completion of the technological developments at the end of the proposed funding cycle, our platform will be ready for testing in human subjects.

心脏病是美国死亡的主要原因;最常见的心脏病类型是由心脏病引起的。 通过动脉粥样硬化、血管壁增厚和动脉粥样硬化斑块的产生。血管内 光学相干断层扫描（IV-OCT）已经能够对冠状动脉结构进行成像， 可用于评价经皮冠状动脉介入治疗的反应 治疗动脉粥样硬化病变时。然而，仍然有一个显着的需要评估斑块vul- 脆弱性：确定哪些轻度病变可能在未来产生心脏事件， 因此需要立即采取预防性干预措施。在病变类型中，薄帽FI- 动脉粥样硬化（TCFA）是特别值得关注的，因为他们被认为是在增加的风险， 然而，研究发现只有一小部分TCFA破裂。尽管 断裂与其机械稳定性、化学成分和微观结构有关， 目前还没有能够对个体患者中的斑块进行生物力学分析的技术 在干预期间[无需耗时的有限元建模（FEM）]， 用于确定组成的可用方法要么缺乏特异性要么缺乏空间分辨率。 为了解决当前血管内成像技术未满足的这一重要需求，我们将开发一种 全光学成像平台，将大大拓宽获得准确的生物力学，化学， 冠状动脉斑块的钙化和微结构分析。我们的新平台将- 能够在目前的综合斑块表征能力方面实现转型性飞跃， 包括牙菌斑组成和易损性的评估。我们将利用新的超快激光 开发每秒2，000帧的IV-OCT，实现了一系列强大的后处理功能 这些技术将增强斑块的全面表征。在目标1中，我们将开发 使硬件能够实现高速血管内成像。在目标2中，我们将开发硬件， 信号处理，以实现10×302 µm3（深度×横向）尺度的微观结构分析，化学 80×802 µm3规模的轮廓，以及全光学中60×602 µm3规模的生物力学轮廓 不需要FEM的技术。在Aim 3中，我们将开发一个基于 软机器人心脏模拟器的生物力学环境的人类跳动的心脏。 我们的单一成像平台将有助于临床研究，以确定斑块vulner的参数- 能力，打开大门，以确定最佳的治疗策略。最初，它将成为一个 动脉粥样硬化的宝贵研究工具;以后，它将有可能指导干预indi- 个别病人。在拟议供资结束时完成技术开发后 周期，我们的平台将准备在人类受试者中进行测试。